Although nontuberculous mycobacteria (NTM), such as Mycobacterium avium-intracellulare complex (MAC), are ubiquitous in the environment, disease caused by NTM is rare in immunocompetent hosts. Localized pulmonary disease, nevertheless, does occur. Most frequently the individuals affected are elderly, non-smoking women. Treatment of pulmonary disease due to MAC in non-HIV-infected patients is typically difficult due to inherent resistance of MAC to anti-tuberculous medications and toxicity. Surgery and/or immunomodulation via cytokine administration have been proposed as potential adjunctive therapies for such patients. In vitro, gamma (y)-interferon (y-IFN) has been shown to enhance killing of MAC by macrophages. Anecdotal evidence suggests that this cytokine may have use in the treatment of MAC disease in humans. For MAC disease limited to the lungs, administration of an aerosolized preparation of y-IFN is appealing because it appears to activate macrophages without producing systemic side effects. In order to gain further insight into the potential utility of y-IFN in the treatment of pulmonary MAC disease, the effect of aerosolized y-IFN on alveolar macrophages will be studied. Specifically, the ability of aerosolized y-IFN to enhance alveolar macrophage binding and killing of MAC will be examined. The information gained from this study will help to determine the potential of y-IFN as an adjunctive therapy for pulmonary MAC in the elderly. If y-IFN appears to be promising in this regard, future investigations can be directed at testing its therapeutic efficacy in pulmonary MAC patients.